The aim of the project proposed in the R03 application is to support additional collaborative research efforts that have become possible as a result of the K23 award, "Comprehensive MR Evaluation of Renovascular Disease" (DK02814). These efforts will improve the likelihood of successful transition of the PI to independent investigator. Broad, long-term objectives/Health-relatedness: In conjunction with anatomic magnetic resonance (MR) imaging, 3D MR renography using Gd-DTPA can improve the specificity of the diagnosis of renal diseases, such as renovascular disease and transplant failure, by identifying and distinguishing between vascular, glomerular and tubular causes of renal dysfunction, and also provide new measures of therapeutic efficacy, SPEC. AIMS: The focus of the R03 proposal is the development of 3D MR renography analysis methods. 1. To develop and refine a multicompartmental model for analysis of MR renographic time-concentration curves recorded from the renal cortex, medulla, and collecting system, and aorta. The model represents the vascular-nephron system as a series of compartments, such as glomeruli, proximal tubules, loops of Henle, distal tubules, and so on, and intercompartmental flow rates correspond to well-known physiologic parameters such as renal plasma flow, glomerular filtration rate, and tubular flow and resorption rates. a. To determine cortical and medullary vascular and tubular compartmental volumes in a sample of nephrectomy specimens by performing detailed morphometric analysis. Estimates of compartmental volumes are scarce in the literature and are necessary for a multicompartmental model. b. To perform a systematic sensitivity analysis of the proposed model to evaluate the sensitivity of the model to changes in parameters as well as to noise in the measured data. 2. To conduct pilot experiments to test the multicompartmental model. By performing maneuvers such as water loading and loop diuretic administration in healthy volunteers, distal tubule and loop of Henle flow rates, respectively, can be selectively affected, and measured changes in renography compared with model predictions. Overall Hypothesis: With a multicompartmental model analysis of 3D MR renography, specific causes of renal insufficiency such as renovascular disease, glomerulopathies, and tubulointerstital diseases can be diagnosed noninvasively with MR imaging.